Calcium and glial cell death

Alberdi, Elena; Sánchez‐Gómez, María Victoria; Matute, Carlos

doi:10.1016/j.ceca.2005.06.020

Cited by 74 publications

(61 citation statements)

References 74 publications

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“…Oligodendrocytes are the major cell type of white matter, which in humans constitutes about 50% of the total brain volume. Oligodendroglia express glutamate receptors and transporters, and are highly vulnerable to excitotoxic and ischaemic insults (for recent reviews see Alberdi et al 65 ) Excessive activation of a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate or NMDA receptors in oligodendrocytes leads to Ca 2 þ overload and cell death. A central event to this process is accumulation of Ca 2 þ within mitochondria, which leads to the depolarisation of this organelle, increased production of oxygen free radicals, and release of proapoptotic factors which activate caspases ( Figure 5).…”

Section: Mü Ller Cells and Retinopathymentioning

confidence: 99%

Glia: the fulcrum of brain diseases

et al. 2007

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Neuroglia represented by astrocytes, oligodendrocytes and microglial cells provide for numerous vital functions. Glial cells shape the micro-architecture of the brain matter; they are involved in information transfer by virtue of numerous plasmalemmal receptors and channels; they receive synaptic inputs; they are able to release 'glio'transmitters and produce long-range information exchange; finally they act as pluripotent neural precursors and some of them can even act as stem cells, which provide for adult neurogenesis. Recent advances in gliology emphasised the role of glia in the progression and handling of the insults to the nervous system. The brain pathology, is, to a very great extent, a pathology of glia, which, when falling to function properly, determines the degree of neuronal death, the outcome and the scale of neurological deficit. Glial cells are central in providing for brain homeostasis. As a result glia appears as a brain warden, and as such it is intrinsically endowed with two opposite features: it protects the nervous tissue as long as it can, but it also can rapidly assume the guise of a natural killer, trying to eliminate and seal the damaged area, to save the whole at the expense of the part. The sudden emergence of an intellect, and therefore a human being, which materialised only around a million years ago, remains the main mystery for our self-understanding. Similarly, we still do not know by which steps or transitions the human intellect emerged from the animal kingdom and where the fundamental difference between a man and an animal lies. According to the neuronal doctrine, which governs modern neuroscience since the beginning of the twentieth century, 1,2 the neurone is regarded as a basic information processing unit consisting of dendrites and axons with a unidirectional flow of information from the receiving dendrites via the integrating cell body to the terminal branches of the axon. Neuronal networks, connected through synaptic contacts, are generally considered as the substrate of our intellect.The number and size of neural cells increase with the size of the body and of the brain of mammals. This increasing quantity eventually has caused the generation of a new quality, the intellect. Rather amazingly, however, there is a relatively little difference in the morphology and physiology of neurones between humans and beasts; similarly the density of synaptic contacts in the brains of rodents and humans is more or less constant at around 1100-1300 millions/mm 3 . 3 On the contrary, evolution of the nervous system resulted in great changes in the second type of neural cells, the neuroglia. 4 Indeed, phylogenetic advance in brain complexity and capabilities coincided with a remarkable increase in the number of glial cells: in the rodent cortex the glial to neurone ratio is about 0.3 : 1, whereas in humans the same ratio is several times higher being B1.65:1, 5 while the total number of glial cells in the human brain is B10 (or even more) times larger than in lesser mammals. Astrocytes ...

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Section: Mü Ller Cells and Retinopathymentioning

confidence: 99%

Glia: the fulcrum of brain diseases

et al. 2007

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“…There is abundant evidence that ATP mediates Ca 21 signals in oligodendrocytes via both P2Y1 and P2X7 receptor subtypes (Alberdi et al, 2005;James and Butt, 2001;Kirischuk et al, 1995). Activation of P2X7 receptors can result in demyelination and the loss of oligodendrocytes and may have a particular role in pathological conditions such as ischemia and MS (see below).…”

Section: Mechanisms For Atp Release In Wmmentioning

confidence: 99%

“…In addition, intercellular Ca 21 waves in astrocytes have been shown to trigger microglial Ca 21 responses through the release of ATP (Schipke et al, 2002;Verderio and Matteoli, 2001), which is central to their injury response (Maeda et al, 2010;Tsuda et al, 2010). Furthermore, ATP is a potent vasoconstrictor and its metabolite adenosine is a potent vasodilator, and so their release by astrocytes at the gliovascular interface could provide a mechanism for local regulation of blood flow, both physiologically and in pathology.There is abundant evidence that ATP mediates Ca 21 signals in oligodendrocytes via both P2Y1 and P2X7 receptor subtypes (Alberdi et al, 2005;James and Butt, 2001;Kirischuk et al, 1995). Activation of P2X7 receptors can result in demyelination and the loss of oligodendrocytes and may have a particular role in pathological conditions such as ischemia and MS (see below).…”

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confidence: 99%

Neurotransmitter signaling in white matter

Butt

Fern

Matute

2014

Glia

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113

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White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates it must have physiological functions other than neuron-to-neuron communication. A surprising aspect is the diversity of neurotransmitter signaling in WM, with evidence for glutamatergic, purinergic (ATP and adenosine), GABAergic, glycinergic, adrenergic, cholinergic, dopaminergic and serotonergic signaling, acting via a wide range of ionotropic and metabotropic receptors. Both axons and glia are potential sources of neurotransmitters and may express the respective receptors. The physiological functions of neurotransmitter signaling in WM are subject to debate, but glutamate and ATP-mediated signaling have been shown to evoke Ca 21 signals in glia and modulate axonal conduction. Experimental findings support a model of neurotransmitters being released from axons during action potential propagation acting on glial receptors to regulate the homeostatic functions of astrocytes and myelination by oligodendrocytes. Astrocytes also release neurotransmitters, which act on axonal receptors to strengthen action potential propagation, maintaining signaling along potentially long axon tracts. The co-existence of multiple neurotransmitters in WM tracts suggests they may have diverse functions that are important for information processing. Furthermore, the neurotransmitter signaling phenomena described in WM most likely apply to myelinated axons of the cerebral cortex and GM areas, where they are doubtless important for higher cognitive function. GLIA 2014;62:1762-1779 Key words: glia, axon, astrocyte, oligodendrocyte, glutamate, ATP Introduction W hite matter (WM) is defined as a tract of myelinated axons-WM appears opaque or dense due to the fatty myelin in anatomical sections and in brain scans. Notwithstanding this, myelination is not restricted to WM and is also critical to rapid communication and integration in grey matter (GM) areas, such as in axons in the cortical GM and hippocampus. Hence, many aspects of neurotransmitter signaling to be covered in this review have resonance in GM and higher cognitive function. Indeed, in the human brain WM is a prominent feature of the cerebral cortex, the seat of higher intelligence. Myelination of GM is also evident in rodents, but discrete WM tracts are not pronounced in the cerebral cortex. As a general concept, WM are simply concentrations of myelinated axons bundled together into tracts that interconnect areas of GM. The molecular physiology of myelinated axons will be very similar in WM and GM, and they will be subject to the same neurotransmitter signaling phenomena that is the subject of this review. The main cells associated with myelinated axons are the myelinating oligodendro...

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“…However, Ca 2ϩ influx across the OL plasma membrane also can occur through a number of other routes: (1) Ca 2ϩ can enter directly through a number of ligandoperated channels; (2) calcium can enter through VOCCs, activated in response to cell membrane depolarization, such as raised extracellular K ϩ ; and (3) depletion of ER stores can result in the opening of store-operated Ca 2ϩ channels (Simpson et al, , 1998Deitmer et al, 1998;Belachew et al, 2000;Alberdi et al, 2005).…”

Section: Cells Overexpressing Golli Exhibit Increased Camentioning

confidence: 99%

Increased Expression of Golli Myelin Basic Proteins Enhances Calcium Influx into Oligodendroglial Cells

Paez¹,

Spreuer²,

Handley³

et al. 2007

J. Neurosci.

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, a specific blocker of voltage-operated Ca 2ϩ channels, abolished the ability of golli to promote process extension in a dose-dependent manner. Analysis of the golli protein identified a myristoylation site at the C terminus of the golli domain, which was essential for the action of golli on Ca 2ϩ influx, suggesting that binding of golli to the plasma membrane is important for modulating Ca 2ϩ homeostasis. High-resolution spatiotemporal analysis along N19 processes revealed higher-amplitude local Ca 2ϩ influx in regions with elevated levels of golli. These findings suggest a key role for golli proteins in regulating voltage-gated Ca 2ϩ channels in OLs during process remodeling. Our observations are consistent with the hypothesis that golli proteins, as a part of a protein complex, modulate Ca 2ϩ influx at the plasma membrane and along OL processes.

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Calcium and glial cell death

Cited by 74 publications

References 74 publications

Glia: the fulcrum of brain diseases

Glia: the fulcrum of brain diseases

Neurotransmitter signaling in white matter

Increased Expression of Golli Myelin Basic Proteins Enhances Calcium Influx into Oligodendroglial Cells

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